Harris, 56, the daughter of immigrants, will take her oath of office at Wednesday's inauguration, marking Day One of the Biden-Harris administration.
She and President-elect Joe Biden will be sworn in with notably increased security and smaller crowds, due to the deadly Jan. 6 attack on the U.S. Capitol and ongoing coronavirus pandemic.
Leading up to her first day in office during this unprecedented time, Harris said she was "filled with a sense of purpose and hope."
"Our country is on a path to heal and to rebuild," she said in a message posted on social media Monday. "Of course, that doesn't mean the road ahead is going to be easy. Our nation continues to face challenges, from the coronavirus pandemic to this economic recession, from our climate crisis to a long-overdue reckoning with racial injustice, to healing and strengthening the democracy that we all cherish."
The vice president-elect will be sworn in by Justice Sonia Sotomayor, another groundbreaking woman -- the first Latina Supreme Court justice.
For the historic day, Harris has chosen to be sworn in using two Bibles. One previously belonged to the late civil rights icon and Supreme Court Justice Thurgood Marshall, someone who inspired Harris' career path. The second belonged to a close family friend, Mrs. Regina Shelton. Harris used Shelton's bible during her swearing-in for the California attorney general's office and the United States Senate.
When Biden announced Harris as his running mate in August, he said, "I know a thing or two about being vice president. More than anything, I know it can't be a political decision. It has to be a governing decision. If the people of this nation entrust me and Kamala with the office of president and vice president for the next four years, we're going to inherit a nation in crisis, a nation divided, and a world in disarray. We won't have a minute to waste. That's what led me to Kamala Harris."
Harris, whose mother was Indian and father is Jamaican, has already achieved several historic milestones throughout her career. She was the first African American woman to be elected district attorney of San Francisco, serving from 2004 to 2010.
In 2011, she became the first woman, first African American and first Asian American to serve as California's attorney general.
Harris represented California as a U.S. senator since 2016 -- the second Black woman and first South Asian American senator in history -- until resigning from the post on Monday. As vice president, she will now preside over the 50-50 Senate and serve as the tiebreaker.
A Harris aide told ABC News this week that they hope that she will not have to break many ties in the Senate, saying that the Biden-Harris team hopes to focus on bipartisan issues.
A graduate of Howard University and the University of California, Hastings College of Law, the Oakland native started her career as a prosecutor in Alameda County and went on to work for the San Francisco city attorney's office, specializing in child sexual assault cases.
As a senator, Harris served on several committees, including the judiciary committee. In that forum, she gained attention using her skills as a prosecutor to grill then-Supreme Court nominee Brett Kavanaugh during his confirmation hearing including about his stance on Roe v. Wade and an alleged decades-old sexual assault, allegations he vehemently denied.
Harris made an unsuccessful run for president in 2019, facing off against Biden in the Democratic primary.
During the first debate of the 2020 election cycle, she caught national attention by challenging Biden on his past stance on busing.
"There was a little girl in California who was part of the second class to integrate her public schools and she was bused to school every day. That little girl was me," Harris said.
Despite the tension between the two during the primary contest, Biden complimented Harris when she suspended her campaign.
"She is a first-rate intellect, a first-rate candidate and a real competitor," he said during an event in Iowa. "I have mixed emotions about it because she is really a solid, solid person and loaded with talent. I’m sure she’s not dropping out on wanting to make the changes she cares about.”
Biden's late son, Beau, who died of brain cancer, had a close friendship with Harris and was a key factor in his choice.
"She had the best recommendation she can get: my son Beau, not a joke,” Biden told "Good Morning America" in August.
Harris' congressional colleagues lauded Biden's choice of running mate.
"For a little girl who grew up poor, Black and female in the South to be considered during this process has been an incredible honor," said Florida congresswoman Val Demings, who was on Biden's shortlist. "I feel so blessed. To see a Black woman nominated for the first time reaffirms my faith that in America, there is a place for every person to succeed no matter who they are or where they come from."
Harris' alma mater, Howard University, called her rise "an important testament of what is possible in our imperfect nation." Adding to the long list of firsts, Harris' victory marked the first time a graduate of a historically black college and university will become vice president.
Her achievements may give way to a new generation of Black female leaders in politics, Nadia Brown, a political science professor at Purdue University, told ABC News in November, upon Harris' historic nomination and election.
"What this symbolically shows is that she is there, she belongs and because of that, generations of other people that have been marginalized also belong," Brown said.
In her first remarks as vice president-elect of the United States, Harris offered an inspirational message of her own.
"While I may be the first woman in this office, I will not be the last. Because every little girl watching tonight sees that this is a country of possibilities," she said in November.
Harris is the author of a memoir, "The Truths We Hold: An American Journey," and a children's book, "Superheroes Are Everywhere."
Her parents, Donald Harris and Shyamala Gopalan, met while attending graduate school at the University of California at Berkeley in the 1960s.
Harris credits her late mother with empowering her to look for solutions.
"I was raised that, when you see a problem, you don't complain about it, you go and do something about it," Harris said in a "Good Morning America" interview.
ABC News' Averi Harper and Beatrice Peterson contributed to this report.